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Biomolecular profiling for noninvasive health monitoring

Nature Biotechnology (2026)Cite this article

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Abstract

Biomolecular profiling offers a powerful lens into human physiology, yet current diagnostics often rely on invasive sampling and delayed, centralized analysis. Advances in mass spectrometry (MS), particularly untargeted metabolomics and proteomics, have expanded molecular access to noninvasive biofluids such as sweat, saliva, tears and interstitial fluid, revealing dynamic biomarkers linked to both chronic and acute conditions. In parallel, wearable biosensors enable real-time, on-body chemical sensing, but remain limited to a narrow panel of predefined analytes. This Review highlights how MS-based molecular discovery and wearable sensing serve as complementary approaches—MS enabling high-dimensional untargeted profiling and wearables delivering longitudinal real-time data—and also discusses how their bidirectional integration and co-evolution open new possibilities for personalized noninvasive health monitoring. We discuss advances in sampling strategies, sensing modalities and system integration, and outline criteria for identifying biomarkers amenable to sensor translation. By uniting untargeted discovery with real-world deployment, this convergence shifts personalized noninvasive healthcare from episodic diagnostics to continuous, context-aware monitoring.

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Fig. 1: From molecular discovery to real-time sensing—an omics-to-wearables translation loop.
Fig. 2: Untargeted metabolomics, lipidomics and proteomics.
Fig. 3: General architecture of wearable chemical biosensors.

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Acknowledgements

This work was supported by the National Institutes of Health (grants R01HL155815 and R33DK132666), National Science Foundation (grants 2145802 and 2444815), Advanced Research Projects Agency for Health (grant ARPA-H-ICHUB-24-101-504), US Army Medical Research Acquisition Activity (grant HT9425-24-1-0249), Army Research Office (grant W911NF-23-1-0041), Office of Naval Research (grant N00014-25-1-2258) and Heritage Medical Research Institute. M.-J.K. was partially supported by the Basic Science Research Program through the National Research Foundation of Korea, supported by the Ministry of Education (RS-2023-00241415).

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Authors and Affiliations

  1. Andrew and Peggy Cherng Department of Medical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA

    Moon-Ju Kim, José A. Lasalde-Ramírez, Wenzheng Heng & Wei Gao

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  1. Moon-Ju Kim
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  2. José A. Lasalde-Ramírez
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  4. Wei Gao
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Contributions

M.-J.K. and W.G. conceived the study and designed the outline and scope. M.-J.K., J.A.L.R., W.H. and W.G. wrote the manuscript.

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Correspondence to Wei Gao.

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W.G. is a cofounder and advisor at Persperity Health. The other authors declare no competing interests.

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Nature Biotechnology thanks Eden Morales-Narvaez, who co-reviewed with Ivan A Lujan-Cabrera; Sihong Wang; and Tiannan Guo for their contribution to the peer review of this work.

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Supplementary Notes 1–3, Supplementary Figs. 1–3 and Supplementary Table 1.

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Kim, MJ., Lasalde-Ramírez, J.A., Heng, W. et al. Biomolecular profiling for noninvasive health monitoring. Nat Biotechnol (2026). https://doi.org/10.1038/s41587-026-03050-2

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